PT  - JOURNAL ARTICLE
AU  - Enchi Liu
AU  - Mark E. Schmidt
AU  - Richard Margolin
AU  - Reisa Sperling
AU  - Robert Koeppe
AU  - Neale S. Mason
AU  - William E. Klunk
AU  - Chester A. Mathis
AU  - Stephen Salloway
AU  - Nick C. Fox
AU  - Derek L. Hill
AU  - Andrea S. Les
AU  - Peter Collins
AU  - Keith M. Gregg
AU  - Jianing Di
AU  - Yuan Lu
AU  - I. Cristina Tudor
AU  - Bradley T. Wyman
AU  - Kevin Booth
AU  - Stephanie Broome
AU  - Eric Yuen
AU  - Michael Grundman
AU  - H. Robert Brashear
AU  - For the Bapineuzumab 301 and 302 Clinical Trial Investigators
TI  - Amyloid-β <sup>11</sup>C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials
AID  - 10.1212/WNL.0000000000001877
DP  - 2015 Aug 25
TA  - Neurology
PG  - 692--700
VI  - 85
IP  - 8
4099  - http://n.neurology.org/content/85/8/692.short
4100  - http://n.neurology.org/content/85/8/692.full
SO  - Neurology2015 Aug 25; 85
AB  - Objective: To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using 11C-Pittsburgh compound B (11C-PiB)-PET.Methods: Two phase 3 clinical trials, 1 each in apolipoprotein APOE ε4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks. PET substudies assessed change in brain fibrillar Aβ over 71 weeks using an 11C-PiB-PET standardized uptake value ratio (SUVr) global cortical average (GCA) comprising the average SUVr from 5 cortical regions of interest with cerebellar gray matter as the reference region.Results: A total of 115 carriers and 39 noncarriers were analyzed. The difference (δ) in mean baseline to 71 week change in 11C-PiB-PET GCA between bapineuzumab and placebo was significant in carriers (0.5 mg/kg vs placebo δ = −0.101; p = 0.004) and in pooled analyses of both carriers and noncarriers (0.5 mg/kg vs placebo δ = −0.068; p = 0.027; 1.0 mg/kg vs placebo δ = −0.133; p = 0.028) but not in the noncarrier trial separately. Analyses by individual region of interest and in mild disease yielded findings similar to the main trial results.Conclusions: The 11C-PiB-PET imaging results demonstrated reduction of fibrillar Aβ accumulation in patients with Alzheimer disease treated with bapineuzumab; however, as no clinical benefit was observed, the findings are consistent with the hypotheses that bapineuzumab may not have been initiated early enough in the disease course, the doses were insufficient, or the most critical Aβ species were inadequately targeted.Aβ=β-amyloid; AD=Alzheimer disease; ARIA=amyloid-related imaging abnormalities; GCA=global cortical average; MMSE=Mini-Mental State Examination; NINCDS-ADRDA=National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association; PiB=Pittsburgh compound B; ROI=region of interest; SUVr=standardized uptake value ratio